GREM1 is epigenetically reprogrammed in muscle cells after exercise training and controls myogenesis and metabolism
GREM1 is epigenetically reprogrammed in muscle cells after exercise training and controls myogenesis and metabolism
Abstract Exercise training improves skeletal muscle function, notably through tissue regeneration by muscle stem cells. Here, we hypothesized that exercise training reprograms the epigenome of muscle cell, which could account for better muscle function. Genome-wide DNA methylation of myotube cultures established from middle-aged obese men before and after endurance exercise training identified a differentially methylated region (DMR) located downstream of Gremlin 1 (GREM1), which was associated with increased GREM1 expression. GREM1 expression was lower in muscle satellite cells from obese, compared to lean mice, and exercise training restored GREM1 levels to those of control animals. We show that GREM1 regulates muscle differentiation through the negative control of satellite cell self-renewal, and that GREM1 controls muscle lineage commitment and lipid oxidation through the AMPK pathway. Our study identifies novel functions of GREM1 and reveals an epigenetic mechanism by which exercise training reprograms muscle stem cells to improve skeletal muscle function.
Grand Fabien Le、Deshmukh Atul S、Barr¨¨s Romain、Pattamaprapanont Pattarawan、Ahwazi Danial、Ingerslev Lars R、Maire Pascal、Moro C¨|dric、Chakroun Imane、Fabre Odile、Brun Caroline、Taleb Anissa、Laurens Claire、Andersen Emil、Parisi Alice、Citirikkaya Kiymet、Rudnicki Michael、Bourlier Virginie、Garde Christian、Giordani Lorenzo、Lundell Leonidas、Mounier R¨|mi、Blais Alexandre
Centre de Recherche en Myologie, Sorbonne Universit¨|, INSFRM UMRS974, Association Institut de Myologie||Institut NeuroMyoG¨¨ne, Universit¨| Claude Bernard Lyon 1, INSFRM U1217, CNRS UMR5534Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen||Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of CopenhagenNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of CopenhagenNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of CopenhagenNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of CopenhagenNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of CopenhagenInstitut Cochin, Universit¨| Paris DescartesINSFRM UMR1048, Obesity Research Laboratory, Institute of Metabolic and Cardiovascular Diseases||University of Toulouse, UMR1048, Paul Sabatier UniversityDepartment of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa||Ottawa Institute of Systems BiologyNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of CopenhagenSprott Centre for Stem Cell Research, Regenerative Medicine Program, Ottawa Hospital Research Institute||Department of Cellular and Molecular Medicine, Faculty of Medicine, University of OttawaCentre de Recherche en Myologie, Sorbonne Universit¨|, INSFRM UMRS974, Association Institut de MyologieINSFRM UMR1048, Obesity Research Laboratory, Institute of Metabolic and Cardiovascular Diseases||University of Toulouse, UMR1048, Paul Sabatier UniversityNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of CopenhagenNestl¨| Institute of Health SciencesNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of CopenhagenSprott Centre for Stem Cell Research, Regenerative Medicine Program, Ottawa Hospital Research Institute||Department of Cellular and Molecular Medicine, Faculty of Medicine, University of OttawaINSFRM UMR1048, Obesity Research Laboratory, Institute of Metabolic and Cardiovascular Diseases||University of Toulouse, UMR1048, Paul Sabatier UniversityNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of CopenhagenCentre de Recherche en Myologie, Sorbonne Universit¨|, INSFRM UMRS974, Association Institut de MyologieNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of CopenhagenInstitut NeuroMyoG¨¨ne, Universit¨| Claude Bernard Lyon 1, INSFRM U1217, CNRS UMR5534Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa||Ottawa Institute of Systems Biology
基础医学生理学分子生物学
Grand Fabien Le,Deshmukh Atul S,Barr¨¨s Romain,Pattamaprapanont Pattarawan,Ahwazi Danial,Ingerslev Lars R,Maire Pascal,Moro C¨|dric,Chakroun Imane,Fabre Odile,Brun Caroline,Taleb Anissa,Laurens Claire,Andersen Emil,Parisi Alice,Citirikkaya Kiymet,Rudnicki Michael,Bourlier Virginie,Garde Christian,Giordani Lorenzo,Lundell Leonidas,Mounier R¨|mi,Blais Alexandre.GREM1 is epigenetically reprogrammed in muscle cells after exercise training and controls myogenesis and metabolism[EB/OL].(2025-03-28)[2025-04-26].https://www.biorxiv.org/content/10.1101/2020.02.20.956300.点此复制
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